This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This study challenges the paradigm that exercise training is not feasible or beneficial in patients with severe peripheral arterial disease. The primary aims of this study are to determine the feasibility and tolerability of 12 weeks, 3 times per week of supervised arm ergometry training on tissue oxygenation of the lower extremities, upper extremity exercise capacity, walking distance, and markers of endothelial dysfunction and inflammation in patients with severe claudication or ischemic rest pain (Critical limb ischemia, CLI). CLI is the most severe form of peripheral arterial disease (PAD), which is caused by progressive atherosclerotic disease that builds up plaque in the arteries of the legs. CLI occurs when there is insufficient blood supply to the tissue of the legs causing pain, even at rest. This insufficiency leads to ischemic rest pain and eventually to ischemic ulcers, gangrene, and even amputation. CLI affects approximately 500-1,000/million individuals per year and uses a significant amount of health care resources. CLI is associated with aging;of the 4.2 million Americans with CLI, 2.5 million are over the age of 70. The overall prognosis for patients with severe peripheral arterial disease is very poor. One year after a diagnosis with critical limb ischemia, approximately 25% of patients will have had an amputation and another 25% will have died. There is a 40% amputation rate and a 40-70% mortality rate over 5 years. Approximately 25 % of individuals with CLI are sufficiently stable so that immediate intervention is not required or they are not suitable for revascularization. These are the potential candidates for alternative therapeutic treatment. There is evidence that upper body exercise improves walking distance and provides additional therapeutic benefits similar to lower extremity exercise. However, there are no known studies that have tested the effect of upper body exercise in individuals with CLI. The systemic response to upper body exercise could have beneficial effects on the lower extremities, resulting in reduction or alleviation of rest pain as well as improvement in markers of systemic inflammation and endothelial dysfunction. This may reduce the need for invasive procedures and decrease the utilization on health care resources. The participants undergo a screening visit where informed consent is obtained, medical history is reviewed, and several quality of life questionnaires are completed. Heart rate, rhythm, and blood pressure are monitored throughout the study. Blood samples are collected before and after exercise, as well as tissue oxygenation in the feet. An ankle blood pressure test that measures circulation to the legs is performed according to established guidelines. The participant then undergoes an assessment of upper extremity aerobic exercise to exhaustion using a hand bike. Respiratory gas measures are collected throughout the test to determine cardiopulmonary fitness and conditioning. A physician supervises all aspects of the testing. The participants are assigned to the exercise or the control group. The exercise group exercises three times per week for 12 weeks using the hand bike at an intensity determined by the initial test. The sessions consist of five minutes of warm up followed by intermittent exercise for 60 minutes followed by five minutes of cool down for a total of 70 minutes. Heart rate and rhythm and blood pressure are monitored throughout the exercise sessions. The control group participants follow their physician[unreadable]s recommendations and continue usual care;these participants are contacted once per month to provide encouragement and to answer any questions that may arise. At the completion of 12 weeks all participants undergo the same testing procedures as during the initial screening visit. This study will provide insight into a cost effective therapeutic option for this functionally debilitated high-risk population, and permit assessment of the feasibility and tolerability, and efficacy of the intervention, all of which will direct subsequent, larger trials.